In order to determine whether functional derangements in hypertrophied myocardium are related to biochemical alterations in the contractile proteins mechanical properties of glycerinated muscle and biochemical characteristics of myosin will be studied in preparations from rabbit hearts during the evolution of experimentally induced hypertrophy. Different types and degrees of cardiac hypertrophy will be produced by constriction of the pulmonary artery, creation of an atrial septal defect, and administration of L-thyroxine. Functional characteristics of the myocardium at different stages of hypertrophy will be studied in isolated papillary muscles. Mechanical properties of the contractile apparatus will be studied in glycerinated muscle prepared from the same hearts, with the use of a myograph with a closed-loop servo system. Myosin from normal and hypertrophied myocardium will be extracted at high ionic strength and purified by ammonium sulfate precipitation, ion exchange chromatography, and ultracentrifugation. The subunit composition of myosin will be analyzed by SDS polyacrylamide gel electrophoresis. Subunits of myosin will be purified by the LiCl-citrate fractionation method and ion exchange chromatography. ATP'ase activities of purified myosin and of recombined myosin subunits will be measured and enzyme activity will be evaluated after incubation under acid and alkaline conditions. Methylation and phosphorylation of the myosin subunits will be examined. Results of these studies should help to elucidate the relationships between altered function of hypertrophied heart muscle and biochemical changes in myosin.